Aryl- and heteroaryl-substituted ureas have been described as inhibitors of cytokine production. These inhibitors are described as effective therapeutics in cytokine-mediated diseases, including inflammatory and autoimmune diseases.
U.S. Pat. No. 6,358,945 describes cytokine inhibiting ureas of the following formula:

An intermediate required to prepare preferred compounds described therein has a 1,4-disubstituted naphthalene as Ar2 and is illustrated in the formula below.

The preparation of these intermediates require the coupling of the naphthyl ring with X. Preferred X include aryl and heteroaryl groups. Previously described methods, including U.S. Pat. No. 6,358,945 achieves the coupling of these aromatic residues by using a coupling reaction catalyzed by a transition metal, such as palladium, in the presence of a ligand, such as triphenyl phosphine. Coupling methods include Stille coupling, requiring the preparation of a tributylstannyl intermediate, or a Suzuki coupling, requiring the preparation of an aryl boronic acid intermediate (Scheme I).

The aryl boronic acid intermediate shown in I has previously been prepared via Br—Li exchange at −70° C. It is desirable to develop a procedure without using cryogenic condition for large-scale or industrial scale production.
Kitigawa et al. disclose a method for preparing trialkyl magnesates useful for halogen-metal exchange (Angew. Chem. Int. Ed. 2000, 39, No. 14 2481–2483). No example in the paper implied the applicability of this method to the preparation of A, which has an acidic proton on the nitrogen.